CD39 Expression Identifies Terminally Exhausted CD8+ T Cells

Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a...

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Published in:PLoS pathogens Vol. 11; no. 10; p. e1005177
Main Authors: Gupta, Prakash K., Godec, Jernej, Wolski, David, Adland, Emily, Yates, Kathleen, Pauken, Kristen E., Cosgrove, Cormac, Ledderose, Carola, Junger, Wolfgang G., Robson, Simon C., Wherry, E. John, Alter, Galit, Goulder, Philip J. R., Klenerman, Paul, Sharpe, Arlene H., Lauer, Georg M., Haining, W. Nicholas
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.10.2015
Public Library of Science (PLoS)
Subjects:
Adenosine
Animals
Antigens
Antigens, CD - immunology
Apyrase - immunology
Arenaviridae Infections - immunology
Biomarkers
CD8-Positive T-Lymphocytes - immunology
Chromatography, High Pressure Liquid
Chronic Disease
Disease Models, Animal
Flow Cytometry
Funding
Hepatitis C, Chronic - immunology
HIV
HIV Infections - immunology
Human immunodeficiency virus
Humans
Infections
Laboratory animals
Lymphocytes
Lymphocytic Choriomeningitis - immunology
Lymphocytic choriomeningitis virus - immunology
Mice
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Pathogens
Population
RNA Virus Infections - immunology
T cell receptors
T-Lymphocyte Subsets - immunology
Transcription factors
Viral infections
ISSN:1553-7374, 1553-7366, 1553-7374
Online Access:Get full text
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Summary:Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion.
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Conceived and designed the experiments: PKG JG DW EJW GML PK AHS WNH. Performed the experiments: PKG JG DW KY KEP CC EA CL. Analyzed the data: PKG JG DW KY KEP EA. Contributed reagents/materials/analysis tools: WGJ SCR GA PJRG. Wrote the paper: PKG JG DW PK AHS GML WNH.
The authors have declared that no competing interests exist.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1005177